One of the general objectives of this research program is to relate the genetic control of serum proteins, especially immunoglobulins, to their chemical structure, biosynthesis and biological function. As a first step, antibody reagents are prepared which identify the allotypic antigenic determinants of the protein and then the genetic control of these determinants are delineated with respect to allelism and linkage. Further, our goal is to assess the distribution of these allotypic specificities among the molecular species of immunoglobulins, i.e. gene expression, in rabbits of various genotype and to localize the allotypic specificities to the polypeptide chain, fragment or domain of the immunoglobulin molecule. Another objective of this research program is to elucidate the mechanism of allotype suppression since we think that this will give us further insight into the mechanism of antibody formation and cell differentiation. The phenomenon of allotype suppression discovered by this investigator makes it possible to develop adult rabbits that are completely devoid of light chains of a particular type (e.g.kappa) or heavy chains or a particular subgroup. At the same time, a compensatory increase occurs so that the total immunoglobulin levels are normal; the increase may occur through an increase in the expression of an allelic gene, a closely linked gene, or an unlinked gene. Allotype suppression is induced by injection of specific antibody to neonatal rabbits but can occur as a result of placental transfer of maternal antibodies. Allotype suppression will be used to develop large amounts of immunoglobulin species ordinarily present in small amounts or perhaps not at all to facilitate the detection of new immunoglobulin allotypes and genes. An in vitro model will be developed so that the mechanism of allotype suppression can be more readily investigated.